The focus of this research is to develop novel bacteriophage display selected ErbB-2 receptor-targeting peptides into 203Pb/212Pb matched pair radiopharmaceuticals for the imaging and therapy of human breast, lung, and ovarian carcinomas. These cancers are a major health concern in the US in that they occur in over 282,000 of our citizens per year and account for 215,000 annual deaths. Previous targeted therapeutics have relied on antibodies which suffer from long biodistribution times, toxicity, and non-target organ radiation damage. We hypothesize that ErbB-2-avid peptides will serve as efficacious well-tolerated imaging and therapeutic agents. AlphaMed is the world leader in the production of alpha-particle radionuclides, such as 212Pb, for use as targeted cancer therapeutics. To better translate 212Pb-based pharmaceuticals into humans, production of a 203Pb-radiolabled beta-emitting ErbB-2-targeting peptide for single photon emission computed tomography (SPECT) imaging of cancer will be vital. In Phase I, we propose to radiolabel the ErbB-2-avid peptide, KCCYSL, with 203Pb, analyze its stability and in vitro breast tumor cell binding properties. In aim 2, we will determine the biodistribution and tumor-targeting properties of 203Pblabeled KCCYSL in vivo in human breast tumor-bearing mice. Results will facilitate treatment planning so that the maximum tolerable activity of the alpha-particle-emitting peptide could be administered. These studies will form the foundation for Phase II studies aimed at developing Pb-based alpha-particle emitting ErbB-2-targeting peptides for the treatment of ovary, lung, and breast cancers.